Patent Application
20220234974
The present invention relates to the hydrogenation of alkynols to alkenols.
Alkynes can be hydrogenated to alkenes by hydrogen in the presence of noble metal catalysts. Palladium catalysts can be used for the hydrogenation of alkynols to alkenols.
Alkynols or the alkenols, respectively, are substances which are produced on an industrial scale and are of high importance, particularly for the field of vitamins and aroma chemicals. A non-exhaustive list of such important alkynols and alkenols are 2-methylbut-3-yn-2-ol, 2-methylbut-3-en-2-ol, 3,7-dimethyloct-6-en-1-yn-3-ol, 3,7-dimethylocta-1,6-dien-3-ol, 3,7,11,15-tetramethylhexadec-1-yn-3-ol and 3,7,11,15-tetramethylhexadec-1-en-3-ol.
In the hydrogenation of alkynols there exist several problems. One problem is that next to the carbon-carbon triple bond also other chemical groups being eventually present might be hydrogenated. To a certain extent this problem can be solved by using protecting groups. This, however, requires additional steps of protection and deprotection which is not favourable in view of additional time, cost and waste formation.
Another problem is that the selectivity at high conversion is not sufficiently high. As in any chemical reaction, the target is to have transformed as much as possible of the starting material into the desired product. In the present case, there is a further drive to obtain as high conversion as possible, because the alkynol, i.e. the starting material, and the alkenol, i.e. the product of the selective hydrogenation, are very difficult to separate. Hence, running reactions at partial conversion followed by separation of the unreacted starting material and repeating the reaction is very difficult.
A particular problematic aspect in the selective hydrogenation of alkynols is the over-hydrogenation. Over-hydrogenation describes the effect that the hydrogenation of alkynol does not stop at the stage of alkenol but continues to yield significant amounts of alkanol, i.e. that the hydrogenation reaction does not selectively only hydrogenate the carbon-carbon triple bond to the carbon-carbon double bond, but that the carbon-carbon double bond is also hydrogenated to a carbon-carbon single bond in significant amounts. The over-hydrogenated compound can be very difficult to be separated from the desired products.
Lindlar discloses in U.S. Pat. No. 2,681,938 a selective hydrogenation of alkynes to alkenes using a palladium catalyst which is modified by lead or bismuth.
In U.S. Pat. No. 3,715,404 a selective hydrogenation is disclosed using a palladium catalyst which is partially deactivated by some specific organic sulphur compounds.
Furthermore, the hydrogenation of alkynols leads to the formation of undesired side products, such as the formation of dimers or oligomers derived from the alkynol or the alkenol.
Therefore, the problem to be solved by the present invention is to offer a process for the hydrogenation of alkynol selectively to an alkenol which yields high conversion, high selectivity and low over-hydrogenation.
Surprisingly, the process according to claim 1 has offered a solution to this problem. It has been found that particularly the use of additives having 2 or more phosphino groups are very advantageous in offering this combination of desired properties.
Further aspects of the invention are subject of further independent claims. Particularly preferred embodiments are subject of dependent claims.
In a first aspect the present invention relates to a process of hydrogenating an alkynol selectively to an alkenol by hydrogen using a hydrogenation catalyst which is palladium supported on a carrier; in the presence of an additive which is an organic phosphorus compound bearing either a phosphino or a phosphine oxide group; characterized in that in case the additive bears a phosphino group that the additive bears two or more phosphino groups.
For sake of clarity, some terms as been used in the present document are defined as follows:
In the present document, a “Cx-yalkyl” group is an alkyl group comprising x to y carbon atoms, i.e., for example, a C1-3-alkyl group is an alkyl group comprising 1 to 3 carbon atoms. The alkyl group can be linear or branched. For example —CH(CH3)—CH2—CH3 is considered as a C4-alkyl group.
Any wavy line in any formula of this document represents a carbon-carbon bond which when linked to the carbon-carbon double bond is either in the Z- or in the E-configuration.
In case identical labels for symbols or groups are present in several formulae, in the present document, the definition of said group or symbol made in the context of one specific formula applies also to other formulae which comprises the same said label.
In the present document, an “alkynol” is a chemical compound which has at least one carbon-carbon triple bond and at least one hydroxyl group in its chemical formula. In other words, an alkynol is a hydroxy functionalised alkyne.
Analogously, an “alkenol” is a chemical compound which has at least one carbon-carbon double bond and at least one hydroxyl group in its chemical formula. In other words, an alkenol is a hydroxy functionalised alkene.
In the present document a “hydrocarbyl” group is a univalent group which formally is formed by removing a hydrogen atom from a hydrocarbon.
In this process an alkynol is selectively hydrogenated to the respective alkenol.
The alkynol has at least one carbon-carbon triple bond and at least one hydroxyl group in its chemical formula whereas the respective alkenol has at least one carbon-carbon double bond and at least one hydroxyl group in its chemical formula.
It is important for the present invention that the hydrogenation is selective, that is reducing the carbon-carbon triple bond to the respective carbon-carbon double bond. In other words, the hydroxyl group as well as any other chemical groups which might be present in the alkynol are not modified by said hydrogenation reaction. Particularly, the hydrogenation is selective also in that sense that the carbon-carbon double bond of the alkenol is not, or at least not significantly, further hydrogenated to a carbon-carbon single bond (“over-hydrogenation”).
It, furthermore, has been observed that—besides the reduced formation of over-hydrogenated products—also the formation of other side products, such as formation of dimers or oligomers derived from the starting material or products, are significantly reduced by the above process.
In one of the preferred embodiments, the alkynol is an alkynol which has a hydroxyl group attached to a carbon which is in alpha position to the carbon-carbon triple bond of the alkynol, i.e. the alkynol is preferably an alpha-alkynol.
The alkynol has preferably a following structural element
in its structural formula, where * signifies the position(s) of further substituent(s).
In an even more preferred embodiment, the alkynol is an alkynol in which the carbon-carbon triple bond is a terminal carbon-carbon triple bond.
In a very preferred embodiment the alkynol has a following structural element
in its structural formula where * signifies the position of further substituent(s).
In a very preferred embodiment the alkynol is an alkynol of the formula (I)
wherein
either
or
In formula (I) the preferred substituent R1 is a methyl group.
It is preferred that R2 represents a saturated linear or branched or cyclic hydrocarbyl group with 1 to 46 C atoms which optionally comprises at least one chemical functional group, particularly at least one hydroxyl group.
It is further preferred that in formula (I) the substituent R2 is a methyl group.
A very preferred alkynol of formula (I) is 2-methylbut-3-yn-2-ol (i.e. R1═R2=methyl).
In another embodiment, R1 and R2 represent together an alkylene group forming a 5 to 7 membered ring. The alkylene group may be linear or branched and optionally comprises at least one chemical functional group, and/or is olefinically unsaturated. It is preferred that alkylene group is not olefinically saturated.
Preferably the alkylene group is a pentylene group. One of the preferred alkynols of this embodiment is 1-ethynylcyclohexan-1-ol.
In another preferred embodiment the substituent is R2 is selected from the group consisting of formula (R2-I), (R2-II), (R2-III), (R2-IV), (R2-V), (R2-VI) and (R2-VII)
The alkynol is preferably an alkynol which is selected from the group consisting of 3-methyl-5-(2,6,6-trimethylcyclohex-1-en-1-yl)pent-1-yn-3-ol, (E)-3-methyl-1-(2,6,6-trimethylcyclohex-1-en-1-yl)pent-1-en-4-yn-3-ol, (Z)-3-methyl-1-(2,6,6-trimethylcyclohex-1-en-1-yl)pent-1-en-4-yn-3-ol, (E/Z)-3-methyl-1-(2,6,6-tri-m ethylcyclohex-1-en-1-yl)pent-1-en-4-yn-3-ol, 3-methyl-5-(2,6,6-trimethylcyclo-hex-2-en-1-yl)pent-1-yn-3-ol, (E)-3-methyl-1-(2,6,6-trimethylcyclohex-2-en-1-yl)pent-1-en-4-yn-3-ol, (Z)-3-methyl-1-(2,6,6-trimethylcyclohex-2-en-1-yl)pent-1-en-4-yn-3-ol, 3,7-dimethyloct-6-en-1-yn-3-ol, 3,7-dimethyloct-1-yn-3-ol, (E)-3,7-dimethylnon-6-en-1-yn-3-ol, (Z)-3,7-dimethylnon-6-en-1-yn-3-ol, (E/Z)-3,7-di-methylnon-6-en-1-yn-3-ol, 3,7-dimethylnon-1-yn-3-ol, 3,7,11-trimethyldodec-1-yn-3-ol, (E)-3,7,11-trimethyldodec-6-en-1-yn-3-ol, (Z)-3,7,11-trimethyldodec-6-en-1-yn-3-ol, (E/Z)-3,7,11-trimethyldodec-6-en-1-yn-3-ol, 3,7,11-trimethyldodec-10-en-1-yn-3-ol, (E)-3,7,11-trimethyldodeca-6,10-dien-1-yn-3-ol, (Z)-3,7,11-trimethyldo-deca-6,10-dien-1-yn-3-ol, (E/Z)-3,7,11-trimethyldodeca-6,10-dien-1-yn-3-ol, 3,7,11,15-tetramethylhexadec-1-yn-3-ol, (E)-3,7,11,15-tetramethylhexadec-6-en-1-yn-3-ol, (Z)-3,7,11,15-tetramethylhexadec-6-en-1-yn-3-ol, (E/Z)-3,7,11,15-tetra-methylhexadec-6-en-1-yn-3-ol, (E)-3,7,11,15-tetramethylhexadec-10-en-1-yn-3-ol, (Z)-3,7,11,15-tetramethylhexadec-10-en-1-yn-3-ol, (E/Z)-3,7,11,15-tetramethyl-hexadec-10-en-1-yn-3-ol, 3,7,11,15-tetramethylhexadec-14-en-1-yn-3-ol, (6E,10E)-3,7,11,15-tetramethylhexadeca-6,10-dien-1-yn-3-ol, (6E,10Z)-3,7,11,15-tetramethylhexadeca-6,10-dien-1-yn-3-ol, (6Z,10E)-3,7,11,15-tetramethylhexa-deca-6,10-dien-1-yn-3-ol, (6Z,10Z)-3,7,11,15-tetramethylhexadeca-6,10-dien-1-yn-3-ol, (E)-3,7,11,15-tetramethylhexadeca-10,14-dien-1-yn-3-ol, (Z)-3,7,11,15-tetramethylhexadeca-10,14-dien-1-yn-3-ol, (6E, 10E/Z)-3,7,11,15-tetramethylhexa-deca-6,10-dien-1-yn-3-ol, (6Z, 10E/Z)-3,7,11,15-tetramethylhexadeca-6,10-dien-1-yn-3-ol, (6E/Z,10E)-3,7,11,15-tetramethylhexadeca-6,10-dien-1-yn-3-ol, (6E/Z,10Z)-3,7,11,15-tetramethylhexadeca-6,10-dien-1-yn-3-ol, (6E/Z, 10E/Z)-3,7,11,15-tetramethylhexadeca-6,10-dien-1-yn-3-ol, (E)-3,7,11,15-tetramethyl-hexadeca-6,14-dien-1-yn-3-ol, (Z)-3,7,11,15-tetramethylhexadeca-6,14-dien-1-yn-3-ol, (E/Z)-3,7,11,15-tetramethylhexadeca-6,14-dien-1-yn-3-ol, (E)-3,7,11,15-tetra-methylhexadeca-10,14-dien-1-yn-3-ol, (Z)-3,7,11,15-tetramethylhexadeca-10,14-dien-1-yn-3-ol, (E/Z)-3,7,11,15-tetramethylhexadeca-10,14-dien-1-yn-3-ol, (6E,10E)-3,7,11,15-tetramethylhexadeca-6,10,14-trien-1-yn-3-ol, (6E,10Z)-3,7,11,15-tetramethylhexadeca-6,10,14-trien-1-yn-3-ol, (6Z,10E)-3,7,11,15-tetra-methylhexadeca-6,10,14-trien-1-yn-3-ol, (6Z,10Z)-3,7,11,15-tetramethylhexadeca-6,10,14-trien-1-yn-3-ol, (6E,10E/Z)-3,7,11,15-tetramethylhexadeca-6,10,14-trien-1-yn-3-ol, (6E/Z,10E)-3,7,11,15-tetramethylhexadeca-6,10,14-trien-1-yn-3-ol, (6Z,10E/Z)-3,7,11,15-tetramethylhexadeca-6,10,14-trien-1-yn-3-ol, (6E/Z,10Z)-3,7,11,15-tetramethylhexadeca-6,10,14-trien-1-yn-3-ol, and (6E/Z,10E/Z)-3,7,11,15-tetramethylhexadeca-6,10,14-trien-1-yn-3-ol.
The process uses a hydrogenation catalyst which is palladium supported on a carrier.
Such hydrogenation catalysts are principally known to the person skilled in the art. Palladium is a noble metal. In the present invention Palladium is supported on a carrier, i.e. palladium is attached to/or deposited on a carrier. The carrier is a solid material.
Preferably said carrier is carbon or an inorganic carrier. Preferred inorganic carriers are oxides or carbonates. Preferred oxides are oxides of silicon, aluminum or titanium or cerium. Particularly preferred are silicon dioxide, alumina and titanium dioxide and ceria.
Silicon dioxide can be used as pyrogenic silica or precipitated or ground silica as carrier. Preferably silicon dioxide used as carrier is pyrogenic or precipitated silica. Most preferred silicon dioxide is a silicon dioxide which is essential pure SiO2. In other words, it is preferred that the silicon dioxide carrier consists of more than 95%, more preferably more than 98%, even more preferred more than 99%, by weight of SiO2.
Calcium carbonate is the preferred carbonate. Preferred calcium carbonate is precipitated calcium carbonate.
It is possible that carrier as used is a mixed oxide.
In addition, the supported palladium catalyst can be doped with other metals, for example lead. A well-known catalyst of this type is the “Lindlar catalyst” which is palladium on calcium carbonate doped with lead. Such Lindlar catalysts are for example commercially available from Sigma-Aldrich, Evonik, Johnson-Matthey or Hindustan Platinum.
More preferred hydrogenation catalysts are palladium on carbon, palladium on silica and palladium on alumina and palladium on carbonate; even more preferred is palladium on calcium carbonate, most preferred is palladium on calcium carbonate doped with lead.
The amount of palladium in the hydrogenation catalyst is preferably in the range of from 0.5 to 20 weight %, more preferably in the range of from 2 to 5 weight %, most preferably in the range of approximately 5 weight %, based on the total weight of the hydrogenation catalyst.
In one the embodiment, the hydrogenation catalyst is used in the form of a colloidal suspension.
Very suitable hydrogenation catalysts are catalysts as they are disclosed in WO 2009/096783 A1 or in Peter T. Witte et al., Top Catal (2012) 55:505-511 and commercialized by BASF under the trade name NanoSelect™.
In another preferred embodiment, the hydrogenation catalyst does not comprise any contain organic any quaternary ammonium compounds.
The process is performed in the presence of an additive which is an organic phosphorus compound bearing either a phosphino or a phosphine oxide group.
In case of the additive bearing a phosphine oxide group it is preferred that said additive has one or two, more preferred one, phosphine oxide group(s).
Particularly preferred as additive which is an organic phosphorus compound bearing a phosphine oxide is diphenylphosphine oxide.
In case of the additive bearing a phosphino group, that said additive has more 2 or more, preferably 2 to 4, more preferably 2 to 3, phosphino group(s).
In a preferred embodiment, the additive has more than one, preferably two, phosphino groups of the formula (III)
The alkyl group is preferably a C1-6-alkyl group. The cycloalkyl group is preferably a C5-8-cycloalkyl group.
In a preferred embodiment the additive is selected from the group consisting of 1,2-bis(diphenylphosphino)ethane, 1,3-bis(diphenylphosphino)-propane, 1,4-bis(diphenylphosphino)butane, 1,3-bis(diphenylphosphino)-2-(diphenylphosphino)methyl-2-methylpropane, 2,2′-bis(diphenylphosphino)-1,1′-binaphthalene and bis(2-diphenylphosphinoethyl)phenylphosphine, preferably selected from the group consisting of 1,2-bis(diphenylphosphino)ethane and 1,3-bis(diphenylphosphino)propane.
The additive can be added as such to the alkynol or as a pre-mixture or as a pre-solution to the alkynol before the beginning of the hydrogenation reaction or added during the hydrogenation process. In case of a pre-solution or a pre-mixture the additive is dissolved or dispersed in a small amount of an organic solvent or, preferably, of the alkynol.
It is preferred that the weight ratio of the additive to catalyst is in the range of 0.01:1-100:1, preferably of 0.1:1-10:1, and more preferably of 0.2:1-3:1.
The amount of hydrogenation catalyst (i.e. sum of palladium and carrier) is preferably in the range of from 0.0001 to 10% by weight %, more preferably in the range of from 0.001 to 1% by weight, most preferably in the range of from 0.01 to 0.1% by weight, based on the weight of the alkynol.
The amount of palladium is preferably 1 to 10% by weight, preferably 3 to 7% by weight, based on the weight of the hydrogenation catalyst.
The hydrogenation reaction is preferably carried out at a temperature in the range of from 10 to 150° C., more preferably at a temperature in the range of from 20 to 100° C., most preferably at a temperature in the range of from 40 to 90° C.
The hydrogenation reaction is preferably carried out at a hydrogen pressure in the range of from 1 to 25 bara (bar absolute) hydrogen, more preferably at a hydrogen pressure in the range of from 2 to 10 bara hydrogen, even more preferably at a hydrogen pressure in the range of from 2 to 6 bara hydrogen, further more preferably at a hydrogen pressure in the range of from 2.5 to 4 bara hydrogen most preferably at a hydrogen pressure in the range of from 2.5 to 3 bara hydrogen.
The hydrogenation reaction can be carried out without solvent or in the presence of an organic solvent. The organic solvent is preferably selected from the group consisting of hydrocarbons, halogenated hydrocarbons, alcohols, ethers, esters, carbonates, amides, nitriles and ketones and mixtures thereof. More preferred are C4-10 aliphatic hydrocarbons, C6-10 aromatic hydrocarbons, C6-10 aromatic hydrocarbons substituted with one or more C1-4 linear alkyl groups or C3-4 branched alkyl groups or halogens, C1-4 linear alcohols or C3-4 branched alcohols, acyclic and cyclic C4-10 ethers, C3-10 esters, C3-10 ketones and mixtures thereof. Especially preferred organic solvents are selected from the group consisting of hexane, heptane, toluene, methanol, ethanol, n-propanol, 2-propanol, n-butanol, tert.-butanol, tetrahydrofuran, 2-methyl-tetrahydrofuran, dioxane, ethyl acetate, isopropyl acetate, ethylene carbonate, propylene carbonate, acetone, and mixtures thereof. The most preferred solvent is heptane.
Preferably, however, the hydrogenation is performed in the absence of any organic solvents.
In a preferred embodiment the hydrogenation is performed in the absence of any organic quaternary ammonium compounds.
In a very much preferred embodiment, the hydrogenation is performed in the absence of any organic solvent and of any organic quaternary ammonium compound.
The above described process yields selectively the respective alkenol. Said alkenol has the same chemical structure as the alkynol, with the exception that the carbon-carbon triple bond is in the alkenol a carbon-carbon double bond.
In other words, when in the preferred case the alkynol of formula (I)
is hydrogenated, the alkenol formed by the selective hydrogenation is the alkenol of formula (II)
with the proviso that R1 has the same meaning in formulae (I) and (II) and that R2 has the same meaning in formulae (I) and (II).
It has been found that the above process of hydrogenating an alkynol selectively to an alkenol that offers at the same time a very high selectivity and very low over-hydrogenation at a very high conversion.
In a further aspect, the present invention relates to a composition comprising
The compound of formula (I), the hydrogenation catalyst as well as the additive have been disclosed and discussed in great detail above.
Said composition is as also disclosed before very suitable to be hydrogenated by molecular hydrogen and yields in very high selectivity the alkenol of the formula (II)
The present invention is further illustrated by the following experiments. List of additives used for the examples:
The hydrogenation catalyst (80 mg, palladium-lead on calcium carbonate containing 5 weight % palladium) was placed in a 500 ml pressure reactor. The respective additive in the amount as given in table 1 and a total of 270 g 2-methylbut-3-yn-2-ol were added to the reactor. The vessel was sealed and purged with nitrogen 3 times (pressurise to 6 bara and release). The reactor was heated to 70° C. and purged with hydrogen 3 times (pressurise to 4 bara and release). The reactor was pressurised to 2.5 bara and the mixture was stirred. The mixture was sampled multiple times near the end of the reaction to determine when the conversion had reached >99.9%. Samples were analysed by GC (area %) to determine the selectivity.
1determined by GC in area %
2selectivity: amount of alkenol in the final reaction mixture
The hydrogenation catalyst (56 mg, palladium-lead on calcium carbonate, containing 5 weight % palladium) was placed in a 500m1 pressure reactor. The respective additive in the amount as given in table 2 and a total of 250 g 3,7-dimethyloct-6-en-1-yn-3-ol were added to the reactor. The vessel was sealed and purged with nitrogen 3 times (pressurise to 6 bara and release). The reactor was heated to 55° C. and purged with hydrogen 3 times (pressurise to 4 bara and release). The reactor was pressurised to 3 bara and the mixture was stirred. The mixture was sampled multiple times near the end of the reaction to determine when the conversion had reached >99.9%. Samples were analysed by GC (area %) to determine the selectivity.
1determined by GC in area %
2selectivity: amount of alkenol in the final reaction mixture
The hydrogenation catalyst (50 mg, palladium-lead on calcium carbonate, containing 5 weight % palladium) was placed in a 500m1 pressure reactor. The respective additive in the amount as given in table 3 and a total of 260 g 3,7,11,15-tetramethylhexadec-1-yn-3-ol were added to the reactor. The vessel was sealed and purged with nitrogen 3 times (pressurise to 6 bara and release). The reactor was heated to 85° C. and purged with hydrogen 3 times (pressurise to 4 bara and release). The reactor was pressurised to 3 bara and the mixture was stirred. The mixture was sampled multiple times near the end of the reaction to determine when the conversion had reached >99.9%. Samples were analysed by GC (area %) to determine the selectivity.
1determined by GC in area %
2selectivity: amount of alkenol in the final reaction mixture
| Number | Date | Country | Kind |
|---|---|---|---|
| 19176760.7 | May 2019 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2020/064496 | 5/26/2020 | WO | 00 |
